The promise and challenge of personalized medicine: aging populations, complex diseases, and unmet medical need

Abstract The concept of personalized medicine is not new. It is being discussed with increasing interest in the medical, scientific, and general media because of the availability of advanced scientific and computational technologies, and the promise of the potential to improve the targeting and delivery of novel medicines. It is also being seen as one approach that may have a beneficial impact on reducing health care budgets. But what are the challenges that need to be addressed in its implementation in the clinic? This article poses some provocative questions and suggests some things that need to be considered

Studies of NGC 6720 with Calibrated HST WFC3 Emission-Line Filter Images--III:Tangential Motions using AstroDrizzle Images

We have been able to compare with astrometric precision AstroDrizzle processed images of NGC 6720 (the Ring Nebula) made using two cameras on the Hubble Space Telescope. The time difference of the observations was 12.925 yrs. This large time-base allowed determination of tangential velocities of features within this classic planetary nebula. Individual features were measured in [N II] images as were the dark knots seen in silhouette against background nebular [O III] emission. An image magnification and matching technique was also used to test the accuracy of the usual assumption of homologous expansion. We found that homologous expansion does apply, but the rate of expansion is greater along the major axis of the nebula, which is intrinsically larger than the minor axis. We find that the dark knots expand more slowly that the nebular gas, that the distance to the nebula is 720 pc +/-30%, and the dynamic age of the Ring Nebula is about 4000 yrs. The dynamic age is in agreement with the position of the central star on theoretical curves for stars collapsing from the peak of the Asymptotic Giant Branch to being white dwarfs

Pumping up the [N I] nebular lines

The optical [N I] doublet near 5200 {\AA} is anomalously strong in a variety of emission-line objects. We compute a detailed photoionization model and use it to show that pumping by far-ultraviolet (FUV) stellar radiation previously posited as a general explanation applies to the Orion Nebula (M42) and its companion M43; but, it is unlikely to explain planetary nebulae and supernova remnants. Our models establish that the observed nearly constant equivalent width of [N I] with respect to the dust-scattered stellar continuum depends primarily on three factors: the FUV to visual-band flux ratio of the stellar population; the optical properties of the dust; and the line broadening where the pumping occurs. In contrast, the intensity ratio [N I]/H{\beta} depends primarily on the FUV to extreme-ultraviolet ratio, which varies strongly with the spectral type of the exciting star. This is consistent with the observed difference of a factor of five between M42 and M43, which are excited by an O7 and B0.5 star respectively. We derive a non-thermal broadening of order 5 km/s for the [N I] pumping zone and show that the broadening mechanism must be different from the large-scale turbulent motions that have been suggested to explain the line-widths in this H II region. A mechanism is required that operates at scales of a few astronomical units, which may be driven by thermal instabilities of neutral gas in the range 1000 to 3000 K. In an appendix, we describe how collisional and radiative processes are treated in the detailed model N I atom now included in the Cloudy plasma code.Comment: ApJ in press. 8 pages of main paper plus 11 pages of appendices, with 13 figures and 12 table

Rotationally Warm Molecular Hydrogen in the Orion Bar

The Orion Bar is one of the nearest and best-studied photodissociation or photon-dominated regions (PDRs). Observations reveal the presence of H2 lines from vibrationally or rotationally excited upper levels that suggest warm gas temperatures (400 to 700 K). However, standard models of PDRs are unable to reproduce such warm rotational temperatures. In this paper we attempt to explain these observations with new comprehensive models which extend from the H+ region through the Bar and include the magnetic field in the equation of state. We adopt the model parameters from our previous paper which successfully reproduced a wide variety of spectral observations across the Bar. In this model the local cosmic-ray density is enhanced above the galactic background, as is the magnetic field, and which increases the cosmic-ray heating elevating the temperature in the molecular region. The pressure is further enhanced above the gas pressure in the H+ region by the momentum transferred from the absorbed starlight. Here we investigate whether the observed H2 lines can be reproduced with standard assumptions concerning the grain photoelectric emission. We also explore the effects due to the inclusion of recently computed H2 + H2, H2 + H and H2 + He collisional rate coefficients.Comment: Accepted for publication in ApJ (34 pages, including 16 figures

In silico clinical trials: how computer simulation will transform the biomedical industry

The term ‘in silico clinical trials indicates the use of individualised computer simulation in the development or regulatory evaluation of a medicinal product, medical device, or medical intervention. This review article summarises the research and technological roadmap developed by the Avicenna Support Action during an 18 month consensus process that involved 577 international experts from academia, the biomedical industry, the simulation industry, the regulatory world, etc. The roadmap documents early examples of in silico clinical trials, identifies relevant use cases for in silico clinical trial technologies over the entire development and assessment cycle for both pharmaceuticals and medical devices, identifies open challenges and barriers to a wider adoption and puts forward 36 recommendations for all relevant stakeholders to consider